NOVEL COMPOUNDS

Abstract: Novel antibiotic compounds being tricyclic sesquiterpenes of formula (I) and derivatives thereof are described, wherein R<1>, R<2>, R<3>, R<4> and R<5> independently are the same or different substituents chosen from the group comprising =O, -OH, -OR, where R is straight or branched C1-12 alkyl, and straight or branched C1-12 alkyl, and Z means a single or double bond.

Description: Title: NOVEL COMPOUNDS FIELD OF THE INVENTION The present invention relates to novel compounds being tricyc- lic sesquiterpenes and derivatives thereof. The compounds of the invention have antibiotic activities, e- specially antibacterial activity. The compounds of the invention may be produced by culturing certain Streptomyces species and recovering at least one of the compounds of the invention, which subsequently may be derivati- zed, if appropriate. The compounds of the invention may be used as biocidal prepa¬ rations, either alone or in combination with other biocides in admixture with acceptable excepientε suitable for the applica- tion in question. BACKGROUND OF THE INVENTION The majority of known terpenoids are produced by eukaryotic organisms. However, a variety of actinomycetes, most notably members of the genus Streptomyces, produce sesquiterpenes which have been implicated in the production of earthy odours in water 1 ' 2 , and in soil 3 . These were identified as geosmin, methyl- isoborneol in combination with the heterocyclic 2-isopropyl-3- ethoxy-pyrazine 4 . Other odorous sesquiterpenes have been isola¬ ted from broths of streptomycetes and include cadin-4-ene-l-ol 5 , εelina-4 (14) ,7 (11) -diene-9-ol(1)° and mucidone 7 . The antibiotic, arenamycin, is one of the few sesquiterpenes produced by strep- tomycetes reported to have biological activity 8 . This metaboli¬ te, also known as pentalenolactone, is biosynthesized via the enzymatic cyclization of farnesyl pyrophosphate to pentalene 9 . The current and practical relevance of actinomycetes in Bio¬ technology has been emphasized in "Actinomycetes in Biotech¬ nology" eds. M. Goodfellow, S.T. Williams & M. Mordarski, 1988. SUMMARY OF THE INVENTION The present invention relates to novel compounds having the general formula (I) (I) wherein R 1 , R 2 , R 3 , R , and R 5 independently are the same or different substituents chosen from the group comprising =0, - OH, -OR, where R is straight or branched 1- 12 alkyl and straight or branched C 1 _ 12 alkyl, and Z means a single or double bond, and derivatives thereof. The compounds of the invention have antibiotic activities, especially antibacterial activity, but it is also believed that compounds of the invention may have other activities, such as fungicidal and/or insecticidal activities. The compounds of the invention may be produced by culturing certain Streptomyces species and recovering at least one of the compounds of the invention, which subsequently may be derivati- zed, if appropriate. Especially the compound with the formula (III) , which we have named albaflavenone may be produced by the strain DSM 5415, which phenotypically has been characterized as belonging to the species-group Streptomyces albidoflavus . Albaflavenone may be recovered and derivatized according to known techniques. The compounds of the invention may be used as biocidal prepa¬ rations, either alone or in combination with other biocides in admixture with acceptable excepients suitable for the applica¬ tion in question. It has been envisaged that compounds of the invention may be applied in the human and veterinary medicine, within agricul- ture in general, and as a disinfectant for cleaning various equipment. DETAILED DESCRIPTION OF THE INVENTION The invention is based on the isolation of an unusually odor¬ iferous actinomycete which produces a novel sesquiterpene, albaflavenone, identified as 2, 6,7,7-tetramethyltricyclo[6.- 2.1.0 I,5 ]undec-5-en-4-one. The characteristics of this strain together with the isolation and identification of the novel metabolite and its antibiotic activity are described below. The present invention relates in one aspect to novel compounds having the general formula (I) (I) wherein R 1 , R 2 , R 3 , R , and R 5 independently are the same or different εubstituents chosen from the group comprising =0, - OH, -OR, where R is εtraight or branched C 1 _ 12 alkyl, and straight or branched C 1 _ 12 alkyl, and Z means a single or double bond, and derivatives thereof. Preferred compounds of the invention have the formula (II) (II) wherein R 1 , R 3 , R 4 , and R 5 independently are the same or dif¬ ferent substituentε choεen from the group compriεing εtraight or branched C 1 _ 12 alkyl, and derivatives thereof. The compounds of the invention have antibiotic activities, especially antibacterial activity, but it iε also believed that compounds of the invention may have other activities, such as fungicidal and/or insecticidal activities. The compounds of the invention may be produced by culturing certain Streptomyces species and recovering at least one of the compounds of the invention, which subεequently may be derivati- zed, if appropriate. Eεpecially the compound with the formula (III) , which we have named albaflavenone may be produced by the strain DSM 5415, which phenotypically has been characterized as belonging to the specieε-group Streptomyces albidoflavus . Albaflavenone may be recovered and derivatized acoording to known techniques. DSM 5415 was in WO92/01038 reported to produce compoundε of inεeticidal and fungicidal activities. Since albaflavenone was isolated from a different fraction of the culture broth from culturing DSM 5415 than the earlier reported activities, albaflavenone iε not a compound respon¬ sible for any of these earlier reported activities. The compounds of the invention may be used as biocidal prepa¬ rations, either alone or in combination with other biocides, mixed with acceptable excepients suitable for the application in question. It has been envisaged that compounds of the invention may be applied in the human and veterinary medicine, within agricul¬ ture in general, and as a disinfectant for cleaning various equipment. EXAMPLES MATERIALS AND METHODS 5 NMR spectra were recorded on a Bruker AMX 600 spectrometer and IR on a Perkin Elmer 1760X FT-IR spectrophotometer. UV spectra originate from a Hewlet Packard 8452A Diode Array instrument and MS on a Jeol JMS-HX/HX 110A tandem masε spectrometer. A Hewlett Packard P 5890 gas chromatograph coupled to a VG 12-250 10 masε εpectrometer waε used for GC-MS investigations. HPLC was monitored with a Hewlett Packard 5880 HPLC detection syεtem. Iεolation and taxonomy of producing εtrain Starch casein medium 10 and the membrane filter method 11 were used 15 for iεolation from seeds. The εtrain, DSM 5415 waε characteri¬ zed and identified uεing the methods of Williams et al . n . A 16S rRNA Streptomyces genus probe aε defined by Stackebrandt et al . 1 waε uεed to confirm generic εtatus of DSM 5415 using the me¬ thod of Stackebrandt et al . 13 . Whole cell hydrolyεateε were ana- 20 lyεed by TLC 14 and chemotaxonomic analyεiε was carried out by the German Collection of Microorganismε and Cell cultures (DSM) and included analyεiε of cell wall amino acidε, menaquinone type and itε abundance in the cytoplaε ic membrane and whole cell fatty acidε. 25 Fermentation Two ml of a εpore εuεpenεion of DSM 5415 were inoculated into 500 ml baffled Erlenmeyer flaεkε containing 100 ml of the me¬ dium which consisted of (g/1) soy tone, 40.0; potato flour, 30 100.0; Na 2 HP0 4 , 12; BAN 120L (Novo Nordisk A/S), 0.2 ml; plu- ronic (antifoam) , 0.2 ml; pH 7.0. The flaskε were incubated at 30°C for 5 dayε at 280 rpm. Isolation of albaflavenone 35 The whole broth (2.5 1) waε extracted with 3x400 lε rediε- tilled EtOAc at pH 6.6. The extract waε dried over MgS0 4 (30 minuteε) and after filtration, concentrated in vacuo . The dried reεidue (2.6 g) waε extracted with 5x10 mlε n-heptane/EtOAc (1/1) , yielding a yellow oil (139 g) , which waε subjected to initial purification on a LiChroprep Lobar Si 60 column of 40- 63 μm (Merck) with EtOAc/n-heptane 2:3. The effluent was moni¬ tored at 260 nm, and each component investigated by GC-MS and by analytical HPLC (RP 18, 5 μm column, acetonitrile/water 80/20) monitored with a photo diode array detector. A fraction (3.2 mg displaying a signal at m/z 218) was further purified by preparative HPLC, using a LiChrosorb Hibar RP 18 column (25x1 cm, 7 μm) with acetonitrile/water 85/15, to give 1.1 mg pure albaflavenone. The following fraction from the inital chromatography (2.8 mg) contained a component with M + at m/z 220, believed to represent the alcohol corresponding to albaflavenone. Further purifica- tion of this fraction gave 400 μg of impure compound which is still under investigation. Tests for antibiotic activity The in vitro activity of albaflavenone was tested against Ba- cillus subtilis ATCC 6633 which was grown in 10 ml tubeε each containing 1 ml of a medium which conεisted of (g/1) Trypticase (BBL) , 20.0; yeaεt extract (Difco) , 5.0; FeCl 2 ; 4H 2 0, 0.006; MnCl 2 ; 4H 2 0, 0.001; MgS0 4 ; 7H 2 0, 0.015; pH 7.3. Different concen¬ trations of pure albaflavenone were added to the tubes. The tubes were incubated at 30°C with shaking (300 rpm) for 20 hours. The lowest concentration that inhibited growth of B . subtilis was recorded as the MIC. Results Taxonomy of producer The producing strain DSM 5415 waε isolated from corn seed. The generic identity was confirmed as Streptomyces by the presence of LL-DAP and glycine in the cell wall and a positive signal was obtained following hybridization of RNA with the 32 P-la- belled 16S rRNA genus probe. The predominant menaquinones were MK-9 (H 4 ,H 6 ,H 9 ) typical for the Streptomyces genuε 15 . However, an atypical feature was noted in the quantitative distribution of MK-9 (H 6 ) , as this is usually the most abundant meaquininone but in DSM 5415 MK-9 (H 4 ) gave the highest peak. This difference was not regarded aε εufficient to affect the generic identification aε the relative abundance of the menaquinoneε haε been εhown to vary with εtageε in the growth cycle 15 . The fatty acid profile εhowed major amountε of the iso- and anteiso-fatty acids cha¬ racteristic of the genuε Streptomyces with major amounts of the fatty acid methyl esterε with chain length 16:0, iso-16:0, anteiso-15: 0, anteiso-17: 0, iso-14:0, iso-15:0, in order of abundance. DSM 5415 produced a εtable mycelium but the long chainε of spores were aggregated into ropes observed by scan¬ ning electron microscopy (SEM) ; theεe ropeε were clearly vi¬ sible under the light microscope. The εubεtrate mycelium and non-εporulating aerial mycelium alεo formed ropeε. Phenotypically DSM 5415 was identified with the εpecieε-group Streptomyces albidoflavus, cluεter 1, with an identification εcore for the Willcox probability of 0.988, taxonomic diεtance (ό") of 0.417 and SE of δ 2.105. The εpore mass was powdery, yellow to cream on all media used for identification teεts. An unusual, εtrong odour waε produced both on solid and in liquid media. DSM 5415 matched to the group S . albidoflavus as defined by Williams et al . 15 in vol. 4 of Bergey's manual, the diagnoε- tic features for which are given by Williams et al . 15 . This positive identification showed that the strain shared the fea¬ tures most diagnoεtic for the group including εpore chain rec- tiflexibleε, ε ooth εpore surface, no production of a diffusible pigment, melanin negative, antibiosis against fungi only (those given in Ref. 15) , positive scoreε for lipolysiε, elaεtin, arbutin and xanthine degradation, resistance to penicillin, 7% NaCl, phenol 0.1%, potasεium tellurite 0.001%, thallous acetate 0.001% and utilization of mannitol. Negative scoreε for diagnostic characters were obtained for presence of soluble pigments and substrate mycelial pigments other than yellow-brown, ability to degrade licithin, pectin, hippurate, resistance to neomycin, growth at 45°C, utilization of 1-hydro- xyproline, 1-rhamnoεe, raffinoεe, dextran and xylitol. The sole atypical character was the inability to produce H 2 S. Further phenotypical details are available in WO 92/01038. Structure elucidation of albaflavenone The colourless solid ketone, named albaflavenone, gave a parent ion in the EI-HR-MS at m/z 218.1664 (Calcd. for C 15 H 22 0: 218.1671) . All fifteen carbon atoms were resolved in the 13 C NMR spectrum (Table 1) . DEPT experiments established the presence of 4 methyl, 4 methylene, 2 methine, and 2 saturated quaternary carbon atoms and three sp 2 hybridized carbon atoms indicating a seεquiterpenoid εtructure. The proton εpin systemε were analyεed uεing ho onuclear decoupling and COSY experimentε. A CH-correlation experiment uεing inverse detection (HMQC sequence 16 ) served to connect the carbon and proton resonanceε as shown in Table 1. According to the 13 C NMR data the three sp 2 - hybridized carbon atoms participate in an α,β-unεaturated ketone moiety. This was substantiated by the UV high intensity band (λ„° H 261 nm, e=7000) compared to findings for Δ 8,14 -ergoste- nol-15-one acetate 17 (λ„^ H 259 nm, e=13,300) and two εtrong IR vibrations ( v KBt 1704 and 1619 cm "1 for C=0 and C=C,respectively) . The remaining three degrees of unsaturation demand the presence of a tricyclic system. The 1 H NMR chemical shift of the allylic C(13)H 3 group (2.09 ppm) predicts this group to reside at the β-position of the α, β unsaturated carbonyl syεtem. Thiε waε εubstantiated by CH- correlation with inverse detection HMQC sequence 16 , optimized for long range couplings, revealing the C(8)H-C(7) (C(14)H 3 ,- C(15)H 3 )-C(6) (C(13)H 3 )=C(5) sequence. The position of the methyl bearing carbonε of thiε sequence was supported by the observa¬ tion of a 2% enhancement of the geminal methyl groups at C(7) by irradiation at the poεition of the εignal originating from C(13)H 3 . The εpin εyεtem C(ll)H 2 -C(8)H-C(9)H 2 -C(10)H 2 lacks cou¬ plings between H(8) and H(9b) and H(llb) . Molecular models demonstrate the C(8)-H bond to be orthogonal to both the C(9)-H b and the C(ll)-H b bonds. C(ll)-H b iε in a "W" relationship to C(10)-H b and C(9)-H b giving rise to long range couplings. The presence of the sequence C(12)H 3 -C(2)H-C(3)H 2 -C(4) was deduced from the data obtained by the inverse detection techniques mentioned above. Further support for these aεsign ents waε obtained from a ROESY experiment (Table 1) . In addition theεe data clarified most of the relative stereochemiεtrieε since crosε peaks between the signalε at 1.75-1.61-1.70 ppm define the cis relationεhip of protons H(9a), H(10a) , and H(lla) . Similarly croεε peaks between the resonanceε at 1.15 and 1.56 and 1.91 ppm, reεpectively, demonstrate the cis relationship between C(14)H 3 , H(llb) and H(8) . Crosε peakε between resonances at 1.12 and 1.79 and 1.91 shows C(15)H 3 to be spatially close to H(9b) and H(8). No cross peaks appeared between the reso¬ nances of H(12)/H(10) and H(2)/H(ll) . However, NOE difference experiments demonstrated enhancement between H(2) and H(llb) and between H(12) and H(10a) . Inspection of models disclose that the enhancements observed are only consiεtent with the propoεed εtructure provided the relative configuration is 1S',2R',8R'. Based on these deductions we aεsign the structure of albaflavenone aε 2R' , 6,7,7-tetramethyl-lS' ,8R'-tricyclo- [6.2.1.0 1-5 ]undec-5-en-4-one analogous to the saturated sesqui- terpene skeleton zizaane (2, 6,7,7-tetramethyl-[6.2.1.0 1,5 ]undeca- ne) . The skeleton of albaflavenone has previously been obtained synthetically from khusimol 18 . The structure of albaflavenone as shown in formula (III) iε not intended to depict the abεolute stereochemistry, which iε at preεent unknown. on Albaf lavenone exhibitε [ α 120 ° (EtOH , c 0 . 024 ) and CD Δe 256 - 2 . 15 and Δe 35ϋ 0 . 87M "1 c-r.-' ( EtOH , 1 . 436 10^M) . GC-MS inveεtigations of the crude EtOAc extract revealed the presence of geosmin identified by compariεon with computerized library data. The characteristic odour of the broth was due to a mixture of geosmin and albaflavenone. The powerful odour of pure albaflavenone is best described as earthy-camphor-like. Table 1 NMR data of albaflavenone Pos. *c *H J ROE 1 51.88 2 33.3d 2.20 6.8 13.27.3 H(3a), H(3b) 103a 47.4t 2.40 7.3 17.3 H(2), H(3b) 3b 2.02 13.2 17.3 H(2), H(3a), H(12) 4 207.4ε 5 138.8ε 6 153.0s 157 42.7s 8 46.2d 1.91 6.85.4 H(9b) , H(lla) , H(14) , H(15) 9a 24.4t 1.75 3.56.811.4 13.8 H(14), H(8), H(10b) 9b 1.79 9.16.3 1.8 13.8 H(8), H(10a), H(lla) 2010a 29.6t 1.61 6.3 11.4 11.3 H(lla), H(9a), H(10b) 10b 1.39 2.39.111.3 H(10a), H(9b) 11a 37.Ot 1.70 5.4 10.9 H(9a), H(10a), H(llb) lib 1.56 1.810.92.3 H(lla), H(14) 12 14.2q 1.07 6.8 H(2), H(3a), H(3b) 2513 13.Oq 2.09 H(15), H(14) 14 28.3q 1.15 H(llb) , H(8) , H(13) , H(15) 15 24.5q 1.12 H(14), H(13), H(8), H(9b) 0 Spectra were measured in CDC1 3 solution at 600 MHz for protonε and at 150.9 MHz for carbon. Chemical shifts are expressed in ppm relative to internal TMS and J in Hz. Biological activity Pure albaflavenone was active against Bacillus subtilis . In the serial dilution assay the MIC for albaflavenone was determined as 8 ~ 10 μg/ml. Further studies of the antimicrobial activity are in progreεε. Discussion The εtrain DSM 5415 waε characteriεed by a novel morphology, which has not previously been described for a streptomycete. Long ropeε of mycelium and εpore chains were formed on a range of media. A further isolate, DSM 6012 was found with the εa e morphology. Studieε of this strain are in progress. Strain DSM 5415 had an atypical menaquinone composition. Major amounts of MK9(H4) were detected. Broth cultures of DSM 5415 had a strong and characteristic odour originating from the seεquiterpenes geosmin and albaflavenone. The latter is an unusual, odorous, volatile metabolite with antibacterial activity. REFERENCES 1) Gerber, N.N.: Volatile subεtanceε from Actinomyceteε: their role in the odour pollution of water. C.R.C. Crit. 5 Rev. Microbiol. 7: 191-214, 1979. 2) Weet, J.; W.Y. Huang & J.L. Laεeter: Streptomyces εp: a εource of odorous substanceε in potable water. Water, Air and Soil Pollution 11: 217-223, 1979. 10 3) Buttery, R.G. & J.A. Garibaldi: Geoεmin and methyliso- borneol in garden soil. J. Agric. Food Chem. 24: 1246- 1247, 1976. 15 4) Gerber, N.N. : Three highly odorous metabolites from an actinomycete: 2-iεopropyl-3-methoxy-pyrazine, methyliso- borneol and geosmin. J. Chem. Ecol. 3: 475-482, 1977. 5) Gerber, N.N. : Sesquiterpenoids from actinomycetes: cadin- 20 4-ene-l-ol. Phytoche istry 10: 185-189, 1971. 6) Gerber, N.N. : Sesquiterpenoids from actinomycetes. Phyto¬ chemistry 11: 385-388, 1972. 25 7) Dougherty, J.D.; R.D. Campbell & R.L. Morris: Actinomy¬ cete: isolation and identification of agent responsible for musty odors. Science 152: 1372-1373, 1966. 8) Koe, B.K.; B.A. Sobin & W.D. Celmer: PA 132, a new 30 antibiotic. I. Isolation and chemical properties. Antibiot. Annu. 672~675, 1956-1957. 9) Cane, D.E.; J.S. Oliver, P.H.M. Harrison, C. Abell, B.R. Hubbard, C.T. Kane & R. Lattman: Biosynthesis of penta- 35 lenene and pentalenolactone. J. Am. Chem. Soc. 112: 4513- 4524, 1990. 10) Williams, S.T. & Wellington, E.M.H. (1982).: Actinomy¬ cetes, Ch 4_5, pp 969-987. In: "Methods of Soil analysis". 40 Part 2. Chemical and Microbiological Properties. 2nd edit (A I Page, R H Miller and D R Keeney, edε) . Amer. Soc. Agronomy Soil Science Soc. America Inc. Pub. Madison, Wisconεin, USA. 45 11) Hirsch, C.F. & D.L. Chriεtensen: Novel method for selec¬ tive isolation of actinomycetes. Appl. Env. Microbiol. 46: 925-929, 1983. 12) Williams, S.T.; M. Goodfellow, E.M.H. Wellington, J.C. 50 Vickers, G.Alderson, P.H.A. Snealh, M.J. Sackin & A.M. Mortimer: A probability matrix for identification of some streptomycetes. J. Gen. Microbiol. 129: 1815-1830, 1983. 13) Stackebrandt,E. , D. Witt, C. Kemmerling, R. Kroppenstedt 55 & W. Liesack; Deεignation of εtreptomycete 16S and 23S rRNA-based target regions for oligonucleotide probes. Appl. Env. Microbiol. 57 (5) : 1468-1477, 1991. 14) Staneck, J.L. & G.D. Roberts: Simplified approach to identification of aerobic actinomycetes by thin layer chromatography. Appl. Microbiol. 28: 226-231, 1974. 15) Williams, S.T., M. Goodfellow & G. Alderson. : Genuε Streptomyceε Waksmans & Henrici 1943, 339AL, pp. 2452- 2492. In Bergey'ε manual of εystematic bacteriology, vol. 4. Ed S.T. Williams, M.E. Sharp and J.G. Holt, The Williams & Wilkins Co., Baltimore, 1989. 16) Bax, A. & S. Subraminian: Senεitivity-enchanced two- dimenεional heteronuclear shift correlation NMR-spectro- εcopy. J. Magn. Res. 67: pp. 565-569, 1986. 17) Stavely, H. E. & G. N. Bollenback: Steroids with Double Bonds between Quaternary Carbon Atoms. I. The Oxidation of α-Ergostenyl Acetate. J. Am. Chem. Soc. 65:1285-1289, 1943. 18) Neuhauε, D. & M. P. Williamson: The Nuclear Overhauser Effect in Structural and Conformational Analysis. VCH Publisherε Inc. Weinhein: 378, 1989. 18) Anderεen, N.H. , Smith, S.E. & Ohta, Y. : Rearrangement of Zizaene-related Sesquiterpenes. J.C.S. Chem.Comm.447-448, 1973.

Claims: PATENT CLAIMS 1. Novel compounds having the general formula (I) (I) wherein R 1 , R 2 , R 3 , R 4 , and R 5 independently are the same or different subεtituentε chosen from the group comprising =0, - OH, -OR, where R is straight or branched C 1 _ 12 alkyl, and straight or branched C 1 _ 12 alkyl, and Z means a single or double bond, and derivatives thereof. 2. The compound of claim 1 having the formula (II) (ID wherein R 1 , R 3 , R , and R 5 independently are the same or different substituentε chosen from the group comprising straight or branched 1 _ 12 alkyl, and derivatives thereof. 3. The compound of claim 2, wherein RI R 3 R 4 and R 5 -ι_i are methyl groups, and derivatives thereof. 4. A procesε for the production of a compound according to any of the claimε 1 to 3 , wherein a bacteria belonging to the species-group Streptomyces albidoflavus is cultivated in the presence of suitable sources for nitrogen and carbon and essen¬ tial nutrients, and the biocidal compound is extracted from the culture broth and recovered according to methods known per se. 5. The proceεs according to claim 4, wherein the bacteria cul¬ tivated is morphologically identical to or exhibits the princi¬ pal morphological features of the bacterial strain deposited under accesεion no. DSM 5415, mutants or genetically engineered variants thereof. 6. The process according to claim 4, wherein the bacteria cul¬ tivated is morphologically identical to or exhibits the princi¬ pal morphological features of the bacterial strain deposited under accesεion no. DSM 6012, mutantε or genetically engineered variants thereof. 7. The procesε according to any of the claims 4 to 6, wherein the compound recovered is a bactericide. 8. The procesε according to any of the claims 4 to 6, wherein the compound recovered is an insecticide. 9. The process according to any of the claimε 4 to 6, wherein the compound recovered iε a fungicide. 10. A biocidal preparation comprising a compound according to any of clams 1 to 3 in admixture with acceptable excepients. 11. The preparation of claim 10 further compriεing at leaεt one further biocide. 12. The preparation of claim 10 or 11 being a bactericidal pre- 5 paration. 13. The preparation of claim 11 or 12, wherein εaid further biocide(s) is a bactericidal agent(s) . 10 14. The preparation of claim 10 or 11 being a fungicidal pre¬ paration. 15. The preparation of claim 10 or 11, wherein said further biocide(s) is a fungicidal agent(s) . 15 16. The preparation of any of claims 10 to 15 being a pharma¬ ceutical preparation for use in treating animalε, including mammalε, and humanε. 20 17. The preparation of any of claimε 10 or 11 being an inεecti- cidal preparation. 18. The preparation of claim 11 or 17, wherein εaid further biocide iε an insecticidal agent. 25 19. The preparation of any of claims 10 to 15, 17 or 18 being an agrochemical preparation for use in treating crops within agriculture, including forrestry. 30 20. A method of controlling microbial infectionε in animals and humanε whereby a preparation according to any of the claimε 10 to 16 is administered to the infected subject. 21. The method of claim 20, wherein εaid preparation is administered topically. 22. The method of claim 20, wherein said preparation is admini- stered systemically. 23. A method of controlling pests in agriculture or forrestry whereby a preparation according to any of the claims 10 to 15, 17, 18, or 19 is applied to the infected area to be treated. 24. The method of claim 23, wherein εaid preparation iε admini- εtered to the εoil prior to emergence of the crop. 25. A method of diεinfecting matter, whereby a preparation ac- cording to any of the claimε 10 to 19 iε applied to the locus to be disinfected.

Inventors: ANTHONI UFFE, GOERTLER HANNE, ANTHONI, UFFE, GOERTLER, HANNE
Applicants: ANTHONI UFFE, GOERTLER HANNE, NOVONORDISK AS, ANTHONI, UFFE, GOERTLER, HANNE, NOVO NORDISK A/S
Application year: 1994
Main classification: C07C49
IPC codes: A01N27, A01N31, A01N35, A01N45, A61K31, A61P31, C07C13, C07C35, C07C49, C12P7, C12R1